General mechanisms of neurotoxicity have been studied with two types of toxin - the parkinsonian syndrome producing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its analogues, and the uncommon plant amino acid 2-amino -3-(methylamino)-propanoic acid (BMAA). The characterization of the toxicity produced by MPTP and its 4'-amino-analogue has shown striatal dopamine depletion in mice and dogs treated with 4-amino-MPTP similar to the specific lesions produced by MPTP. The effects of 4-amino-MPTP could be blocked completely by the monoamine oxidase-B (MAO-B) inhibitor deprenyl, and by the dopamine uptake blocker GBR 12909, suggesting a similar mechanism to that of N=. Studies on the search for substances which immunologically cross-react with antibodies to MPTP or 1-methyl-4-phenyl pyridine in extracts from human brains from parkinsonian or age matched control patients have been completed. Negative correlations were found between patient tissue extracts and those from controls, suggesting the absence of chemically related substances either in the environment or produced as a consequence of a disease process. Mass spectrometric assay of BMAA in cycad seeds and processed flours from Guam was performed in order to test the hypothesis associating BMAA with Guamanian amyotrophic lateral sclerosis/parkinsonism dementia (ALS/PD). The levels of BMAA in plants were reduced by more than 90% by simple washing. However, some of the Guamanian processed flours produced an extract which was more toxic to cultured cells than those prepared in our laboratory due to an added toxic factor. This was characterized as being the inorganic cation zinc, whose high concentration resulted from processing the plants in galvanized containers. This suggests that the association between ALS/PD and cycad flour may be complicated by zinc toxicity in an environment otherwise low in dietary divalent cations. Oxidative damage to neuronal DNA has been implicated in the pathogenesis of neurodegenerative disorders, and to test this hypothesis gas chromatographic-mass spectrometric methods are being developed to quantify modified DNA bases. An assay for thymine glycol has been developed as 2-methylglyceric acid, and is being tested with DNA isolates.